Dasatinib therapy results in decreased B cell proliferation, splenomegaly, and tumor growth in a murine model of lymphoma expressing Myc and Epstein-Barr virus LMP2A

Jamie L. Dargart, Kamonwan Fish, Leo I. Gordon, Richard Longnecker*, Osman Cen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Epstein-Barr virus (EBV) infection and latency has been associated with malignant diseases including nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and immune deficiency associated lymphoproliferative diseases. EBV-encoded latent membrane protein 2A (LMP2A) recruits Lyn and Syk kinases via its SH2-domain binding motifs, and modifies their signaling pathways. LMP2A transgenic mice develop hyperproliferative bone marrow B cells and immature peripheral B cells through modulation of Lyn kinase signaling. LMP2A/λ-MYC double transgenic mice develop splenomegaly and cervical lymphomas starting at 8. weeks of age. We reasoned that targeting Lyn in LMP2A-expressing B cells with dasatinib would provide a therapeutic option for EBV-associated malignancies. Here, we show that dasatinib inhibits B cell colony formation by LMP2A transgenic bone marrow cells, and reverses splenomegaly and tumor growth in both a pre-tumor and a syngeneic tumor transfer model of EBV-associated Burkitt lymphoma. Our data support the idea that dasatinib may prove to be an effective therapeutic molecule for the treatment of EBV-associated malignancies.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalAntiviral Research
Volume95
Issue number1
DOIs
StatePublished - Jul 2012

Keywords

  • Burkitt lymphoma
  • Dasatinib
  • Epstein-Barr virus (EBV)
  • Latent membrane protein 2A (LMP2A)
  • Lyn
  • Post-transplant lymphoproliferative diseases (PTLD)

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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